title: Effect of low dose exposure to the herbicide atrazine and its metabolite on cytochrome P450 aromatase and steroidogenic factor-1 mRNA levels in the brain of premetamorphic bullfrog tadpoles (Rana catesbeiana).
abstract: The transcriptional regulator steroidogenic factor 1 (SF-1) and the enzyme cytochrome P450 aromatase (CYP19) play a central role in modulation of a broad range of tissue-specific developmental processes associated with hormone homeostasis that includes differentiation of the central nervous system. SF-1 and CYP19 expression may be targeted by a variety of endocrine disruptive agents prevalent within the environment. In the present study, we cloned and characterized partial sequences for bullfrog (Rana catesbeiana) SF-1 and CYP19 and examined the effects of a 48h exposure to 1 and 100μg/l of the herbicide atrazine (ATZ) and its major metabolite desethylatrazine (DEA), as well as 5ng/l of the estrogenic chemical, 17α-ethynylestradiol (EE(2)), and 673ng/l of the thyroid hormone, 3,5,3'-triiodothyronine (T(3)), on SF-1 and CYP19 mRNA abundance in the brains of premetamorphic bullfrog tadpoles. Quantitative RT-PCR analysis showed an increase in CYP19 mRNA following a 48h exposure to EE(2) but not T(3) while no significant changes in SF-1 transcript levels occurred. We observed a strong positive correlation between CYP19 and SF-1 transcript abundance in the ATZ-exposed animals which was not evident with DEA- or hormone-exposed tadpoles. Our results are intriguing in light of reported behavioral changes in ATZ-exposed frogs and suggest that further research is warranted to examine the relationship and role of CYP19 and SF-1 in amphibian brain development.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Gunderson
authors.forename: Nik
authors.initials: N
authors.lastname: Veldhoen
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Skirrow
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Macnab
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Graham
authors.initials: G
authors.lastname: van Aggelen
authors.forename: Caren C
authors.initials: CC
authors.lastname: Helbing
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D001280:Atrazine / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003001:Cloning, Molecular; D052244:Endocrine Disruptors / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D006540:Herbicides / Q000633:toxicity*; D007814:Larva / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011892:Rana catesbeiana / Q000235:genetics / Q000502:physiology*; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D029845:Amphibian Proteins; D052244:Endocrine Disruptors; D006540:Herbicides; D012333:RNA, Messenger; D054339:Steroidogenic Factor 1; C405102:desethylatrazine; D014284:Triiodothyronine; D004997:Ethinyl Estradiol; D001141:Aromatase; D001280:Atrazine